There is one non-randomized pharmacological intervention which provides limited additional insight into the utility of sulfonylureas. Ratzmann et al. assigned 27 subjects to the sulfonylurea glibeclamide and diet (n = 27, 2 mg/day) or diet alone (n = 18) in a non-randomized two-year study201. The diet included 30% dietary fat, and limited energy intake only slightly.
At 1 and 2 years, no weight loss occurred in either group. In the analysis, they stratified subjects by level of insulin response to an IVGTT. However, no real differences were seen across these groups. There was a small improvement in glucose tolerance in the low insulin responders, but no changes in fasting or 2 h glucose levels at two years. This study did not find a beneficial effect of sulfonylurea on insulin secretion or glucose tolerance, though the study groups were small. Without randomization or adjustment for baseline differences between groups, it appears that this study, like others conducted in the same period187,195,202, provides limited evidence of benefit for sulfonylureas in prevention or improvement of glucose tolerance. One study which used chlorpropamide did not use controls203 and is not included.
These studies using tolbutamide suffer from a number of methodological weaknesses. However, there are four studies which randomized reasonably large numbers of subjects, who were followed over several years and used intention-to-treat analysis, or reported data that could be calculated this way post-hoc. The study by Feldman et al.187,188 had a substantially lower, though not significantly lower, RR of 0.16 (CI 0.02-1.54). The other widely quoted study by Sartor et al.196 also had non-significant risk reductions when analyzed by intention to treat (RR = 0.82 (CI 0.27-2.50) vs. placebo, RR = 0.73 (CI 0.25-2.14) versus diet, post-hoc analyses). The Bedford study194 was also of 10 years duration, and found no decrease in risk (OR = 1.04), which is consistent with the prior studies, given their wide confidence intervals. The six-year follow-up of the FHS-II200 does not support an effect on diabetes incidence using current fasting criteria, and the effect on 'overt diabetes' (fasting glucose >180 mg/dL, 10 mmol/L) may simply be a treatment effect of the drug. The remaining studies were essentially negative or uninformative. Thus, the current evidence does not support a consistent role for tolbutamide derivatives in the prevention of type 2 diabetes.
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All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.